Genetic mechanism of aerobic capacity in Rat Model
My current research is metabolic disease on rat disease model. We aim to provide a better understanding of metabolic disease and a model for therapy.
Aerobic capacity refers to the max amount ability of oxygen consuming during exercise. It is a function of overall performance of cardiorespiratory system, and has strong association of risks of obesity, hypertension, and type-2 diabetes. We adopted a rat model system, comprising with two lines with well established phenotype on running ability. After directional selection on running ability for >= 30 generations, two lines, HCR (high capability runners) and LCR (low capability runners), display a distinguished heterogeneous phenotype and dramatic diversified physical features, although sharing with a common ancestors. Combine with transdisciplinary approaches, with massive microarray and sequencing tools, we are now deciphering the genetic basis for aerobic capacity.
Diversification and evolution of tumor cells
My Ph.D thesis focuses on the evolutionary issue of cancer genome, including the diversification of tumor cells and evolution of mutation rate. We aim to expand our knowledge of macro-level population genetics to micro-level tumor cells in order to extend framework of classical evolutionary theory to cellular level.
In 1976, Peter Nowell proposed a remarkable perspective on cancers as an evolutionary process at cellular level. Analogy to modern Darwinian Theory, the most important issue is whether the accumulated mutations adaptive for cellular process. Our research is based on the diversification between metastasis and primary tumors, aiming to reveal whether cellular heterogeneity an adaptive or drift biological process. We have paired hepatocellular carcinoma samples and validate at a small number of cells. My work includes: 1) identify rapid clones and its causing mutations 2) simulate population dynamics between adenoma and carcinoma. Our results show a strong phenomenon of selection for certain mutations during metastasis. Besides this, further results in adenoma and paired carcinoma indicate a pathway selection during the evolution of cancer cells.
Evolution of Mutation Rate in vivo
I consider mutation rate as one of my long term interest, as the essential and basic position in population genetics. Mutation rate is a product with multiple effects, and the evolution of mutation rate in cancerous cells is a representative issue, not only demonstrates the genetic basis of cancer, but also tests the hypothesis in cellular level. With the analysis of cancer genomic data, I describe the profiling of mutation rate and identify the significance of mutator effect. My work includes: 1) the effect of internal factor on mutation number variations, namely “intrinsic mutator”, 2) reveal the evolution of time-series mutation rate. My results show that the existence of internal driving factors and “mutator” effect could contribute largely to the accumulation of somatic mutations.
Previous Lab Experience
During my fantastic campus life in Wuhan University from 2003 to 2007, I worked mainly for two aspects, group-I intron and Metarrhizium anisopliae in labs of Dr. Zhang Yi and Dr. Hu Yuanyang. I received my first published paper in 2006 in Zhang's lab, which is a milestone in my scientific career. Dr. Zhang had a beneficial influence on my scientific life with her scientific spirit. Then, I steeped into CAS(Chinese Academy of Sciences) for senior scientific training from 2007 to 2012. In 2008, I studied in BGI, supervised by Dr.Wang Jun, who showed me another view of scientific view, which is a large fortune for me. From 2009 on, Dr. Wu Chung-I guided me to the world of evolution and population genetics.